Summary V114i NKT cells have been implicated in the regulation of immune responses associated with a broad range of diseases, including autoimmunity, infectious diseases and cancer. Their regulatory functions are thought to be mediated by their action on other cells of the immune system, yet the nature of the putative interactions among these cells in vivo during the immune response is totally unknown. V114i NKT cells behavior in situ represents a new area of investigation that has been vastly ignored because of the lack of tools necessary to uniquely track these cells. We propose to generate a new transgenic mouse model that will allow for the visualization of labeled-V114i NKT cells among unlabeled "conventional" T cells. This situation will recapitulate as closely as possible the "normal" repertoire of wild-type animals and will permit the study of the in situ behavior of V114i NKT cells in resting animals. PUBLIC HEALTH RELEVANCE Natural Killer T cells (NKT cells) play an important role in regulating a variety of immune responses. Several major advances have been made in the recent years regarding how these cells develop, recognize their antigens and influence immune responses. Yet, the localization of this lymphocyte population in tissues and its migratory behavior remains unexplored. This is largely due to the lack of reagents and models to unambiguously identify this cell population directly in vivo. The proposed studies aim at producing an animal model that will allow for the visualization of the NKT cell population directly in vivo. An understanding of NKT cell localization and trafficking in tissues could potentially be exploited for therapeutic usage to improve human health.